TY - JOUR
T1 - Urokinase plasminogen activator/urokinase-specific surface receptor expression and matrix invasion by breast cancer cells requires constitutive p38α mitogen-activated protein kinase activity
AU - Huang, Shuang
AU - New, Liguo
AU - Pan, Zhixing
AU - Han, Jiahuai
AU - Nemerow, Glen R.
PY - 2000/4/21
Y1 - 2000/4/21
N2 - Overexpression of urokinase plasminogen activator (uPA) and its receptor (uPAR) has been well documented in a wide variety of tumor cells. In breast cancer, expression of uPA/uPAR is essential for tumor cell invasion and metastasis. However, the mechanism responsible for uPA/uPAR expression in cancer cells remains unclear. In the studies reported here, we show that endogenous p38 MAPK activity correlates well with breast carcinoma cell invasiveness. Treatment of highly invasive BT549 cells with a specific p38 MAPK inhibitor SB203580 diminished both uPA/uPAR mRNA and protein expression and abrogated the ability of these cells to invade matrigel, suggesting that p38 MAPK signaling pathway is involved in the regulation of uPA/uPAR expression and breast cancer cell invasion. We also demonstrated that SB203580-induced reduction in uPA/uPAR mRNA expression resulted from the destabilization of uPA and uPAR mRNA. Finally, by selectively inhibiting p38α or p38β MAPK isoforms, we demonstrate that p38α, rather than p38β, MAPK activity is essential for uPA/uPAR expression. These studies suggest that p38α MAPK signaling pathway is important for the maintenance of breast cancer invasive phenotype by promoting the stabilities of uPA and uPAR mRNA.
AB - Overexpression of urokinase plasminogen activator (uPA) and its receptor (uPAR) has been well documented in a wide variety of tumor cells. In breast cancer, expression of uPA/uPAR is essential for tumor cell invasion and metastasis. However, the mechanism responsible for uPA/uPAR expression in cancer cells remains unclear. In the studies reported here, we show that endogenous p38 MAPK activity correlates well with breast carcinoma cell invasiveness. Treatment of highly invasive BT549 cells with a specific p38 MAPK inhibitor SB203580 diminished both uPA/uPAR mRNA and protein expression and abrogated the ability of these cells to invade matrigel, suggesting that p38 MAPK signaling pathway is involved in the regulation of uPA/uPAR expression and breast cancer cell invasion. We also demonstrated that SB203580-induced reduction in uPA/uPAR mRNA expression resulted from the destabilization of uPA and uPAR mRNA. Finally, by selectively inhibiting p38α or p38β MAPK isoforms, we demonstrate that p38α, rather than p38β, MAPK activity is essential for uPA/uPAR expression. These studies suggest that p38α MAPK signaling pathway is important for the maintenance of breast cancer invasive phenotype by promoting the stabilities of uPA and uPAR mRNA.
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U2 - 10.1074/jbc.275.16.12266
DO - 10.1074/jbc.275.16.12266
M3 - Article
C2 - 10766865
AN - SCOPUS:0034697159
SN - 0021-9258
VL - 275
SP - 12266
EP - 12272
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 16
ER -